Tag: memory

When was your first kiss? What were you doing the last time you heard life-changing news? After only a single experience, your brain was somehow able to form a long-term memory of these events. This phenomenon has baffled neuroscientists for decades, but in a recent paper published in PNAS, Yamagata et al. report a surprising discovery that may finally provide some answers.

Scientists have long thought that memory storage follows a standard path: short-term memory is stored in one part of the brain, then eventually strengthened and transferred into long-term storage somewhere else. This transfer from short- to long-term memory typically requires repetition (think of memorizing song lyrics or studying for an exam). So how, then, does your brain form a long-term memory after a single momentous event?

Figure 1. Flies can learn that a particular odor is associated with a reward. (1) Fly trained with odor and sugar reward, (2) Fly trained with odor and researcher-activated reward neurons.

Imagine that you are a starving fruit fly, desperately searching for food in a new area. Suddenly, you encounter a mysterious new odor and discover a nearby source of life-sustaining food. After a single experience such as this, flies can instantly form an association between that new odor and food, and will follow the odor if it encounters it again (Figure 1-1). Yamagata et al. took advantage of this instinctual behavior to study how the fly brain stores a long-term memory after one event.

They trained groups of flies to associate a particular odor (A) with a sugar reward by presenting them with both stimuli at the same time. They confirmed that the flies formed a memory by giving them a choice between odor A and a different odor (B), and found that flies preferably flocked to an area scented with odor A.

They also identified a large group of dopamine neurons (known as PAM neurons) that were activated by the sugar reward. If the researchers activated the PAM neurons instead of providing sugar when the flies encountered odor A, the flies still associated that odor with a reward (Figure 1-2).

Now the question: how does PAM neuron activity paired with an odor form a long-term memory? The researchers found that the PAM neurons could actually be grouped into two types. When they activated one type, which they dubbed stm-PAM, the flies only formed a short-term memory. The researchers tested their memory immediately after training and found most of the flies hanging around odor A. But 24 hours later, the memory was gone.

Surprisingly, when the researchers activated the other type of PAM neurons during training (called ltm-PAM), the flies only formed a long-term memory! The flies weren’t particularly interested in odor A immediately after training, but 24 hours later the flies flocked toward it. This incredible result showed that long-term memory doesn’t necessarily require a short-term counterpart. So, instead of the reward pathway forming a short-term memory that later transforms into a long-term memory, this sugar reward formed two complementary memories.

Figure 2. Long-term memory (LTM) doesn’t always form from short-term memory (STM). In some cases, STM and LTM form independently, with STM degrading over time, and LTM progressively strengthening.

How can you have a long-term memory without a short-term memory? Imagine again that you are a starving fly, and you just ate something that didn’t taste very good. You’ve moved on, but later realize that you feel satisfied and energetic. You didn’t form a rewarding short-term memory because the food wasn’t very tasty, but now you have a positive long-term memory because it was nutritious. This is precisely what the researchers discovered when they investigated the PAM neurons further.

The researchers trained the flies using arabinose, an artificial sweetener that tastes sweet but isn’t nutritious, and sorbitol, a nutritious but tasteless sugar. Flies that ate arabinose formed a short-term memory that required stm-PAM activity, while the flies that ate sorbitol formed a long-term memory that required ltm-PAM activity. Thus, the researchers found that the PAM neurons seem to carry two separate pieces of information about the sugar reward: a “delicious” signal, which creates a short-term rewarding memory, and a “nutritious” signal, which creates a long-term memory.

These findings show that long-term memory doesn’t always form from a short-term memory. Instead, they can be independent processes created from different information signals about the same stimulus, such as taste and nutrition from sugar. In humans, our rewards are even more complex (such as the feelings associated with your first kiss), and our memory system likely works in a similar way.

Valentine’s Day is quickly approaching, which means that men (and women) all over the U.S. are performing courtship rituals to woo a companion. But while we humans often have trouble figuring out the right moves to attract a potential mate, fruit flies have it down to a science. And incredibly, researchers can study fruit fly courtship to gain a better understanding of our own brains.

In polite fruit fly society, males have the responsibility of wooing a female. The mating behavior is composed of several specific steps (see figure), which the males perform in repetition until the female responds (or until the male gives up trying). This courtship behavior is very well understood by researchers, due in part because the courtship ritual is so stereotyped and predictable. Courtship is a complex innate behavior, which means that all flies are born with the knowledge of how to do it. Successful mating means passing your genes on to the next generation, so the networks of neurons responsible for this behavior are critical for survival and therefore consistent among flies. This consistency provides a perfect system for studying how neurons interact to give rise to a behavior.

Fly researchers have made great progress in unraveling the anatomy underlying courtship, and found that the behavior arises from the integration of multiple sensory cues, including smell (is the female releasing “come and get me” pheromones?), vision (does the female look interested?), and touch (am I in the right spot?). The fruit fly brain has to combine all of this information to influence the fly’s decision making. Should he start the next step of the courtship ritual, or try this one again? Can he approach the female and try to mate?

“But who cares about fruit fly sex?” you might ask. The fly researchers studying courtship aren’t necessarily interested in exactly how flies get it on. They’re more interested in a general understanding of how the brain integrates multiple sensory cues to influence decisions. The fact that the “courtship circuit” is critical for survival suggests that it is also used by other important behaviors, and is shared by other species. Think about how much information needs to be integrated for you to hunt for food, drive a car, or even court another human. The complexity is amazing… how does our brain manage that?! By first studying it in the simpler brains of fruit flies, we can gain a basic understanding that we can apply to our complex mammalian brains.

Studying courtship behavior can provide us with an understanding for how neurons communicate and integrate information to make decisions, but researchers can do even more with it. As our understanding of courtship increases, we can use it to investigate other behaviors that seem more directly related to human health, such as learning and memory, sleep, and addiction.

For example, the courtship ritual is most commonly used to study memory. Researchers have noticed that male flies tend to “give up” after too many rejections, so they’ve developed a learning experiment that exposes males to uninterested females. Normal males quickly learn to give up on trying to mate with them, but what happens if a scientist mutates a particular gene or “turns off” a certain molecule? Now researchers can use courtship to investigate the genes and molecules involved in learning and memory. If a mutant male never learns to stop courting, the gene might be involved in learning. If the mutant male initially learns to give up, but then quickly forgets the experience and tries again, the gene might be involved in long-term memory.

The predictable steps of courtship also allows researchers to easily recognize when a male is impaired in this innate behavior, providing a system for studying brain development. Last year, the Seghal lab published a study in which they used courtship behavior to show that sleep is necessary for normal brain development. They deprived young flies of sleep and found that, as adults, the flies were impaired in courtship. The impairment was due to lack of growth in a brain region important for the behavior, suggesting that sleep deprivation stunts brain development.

As a final example (and one of my favorites), in 2012 the Heberlein lab produced a paper showing that sexual rejection makes male flies turn to booze. Natural rewards such as sex activate the brain’s reward system, which is also activated by abused drugs and alcohol (did you know that flies can be alcoholics too?). Understanding how natural rewards, drugs, and rejections affect the reward system is important for treating or preventing addiction. From this study, the researchers in the Heberlein lab found that levels of neuropeptide F (NPF), a signaling chemical, rose and fell with reward and rejection. Low levels of NPF drove flies to drink, and artificially raising NPF levels prevented this behavior. Their finding that the same chemical is involved in both natural and artificial rewards directly helps research aimed at understanding a similar chemical in mammals called NPY.

In these research examples, the goal of studying courtship wasn’t to learn about fruit fly sex, it was to use what we know to answer more important questions. Because of these studies, researchers have identified dozens of genes and molecules involved in learning and memory, uncovered more reasons for why sleep is important, and progressed our understanding of how alcohol affects the brain. All of these findings have direct implications for human health because we also share those memory genes, need sleep, and use drugs and alcohol.

So the next time you see some flies getting it on near your bananas… swat them, because they’ll make hundreds of new nuisances for you to deal with. But afterward, you can smile knowingly to yourself and remember that scientists are studying the act to answer long-standing questions in neuroscience.

Researchers at Brandeis University have found that the link between sleep and memory is stronger than we thought. It is well known that sleep is important for learning and memory, and many people can attest to having a hard time focusing and remembering things after a bad night’s sleep. Students often receive advice about getting a good night’s sleep instead of late-night cramming before a test. Simply put, scientists have learned that the brain takes advantage of the quiet hours during sleep to transfer newly-learned memories into long-term storage.

But how exactly are these complex behaviors connected in the brain? Does sleep simply permit memory storage to take place, such that the part of the brain involved in memory just takes advantage of sleep whenever it can? Or are sleep and memory physically connected, and the same mechanism in the brain is involved in both? In a recent study published in eLife, researchers in the Griffith lab may have finally uncovered the answer. They found that a single pair of neurons, known as the DPM neurons, are actively involved in both sleep and memory storage in fruit flies.

Why the fly? Fruit flies may be less complex than humans, but they have similar behaviors such as sleep and memory, and their brains have a similar organization. You may have heard of the hippocampus: the seahorse-shaped brain region in mammals that is responsible for learning and memory. The hippocampus receives a lot of information from other parts of the brain, and it has been very difficult for researchers to sort it all out. Fortunately, fruit flies have a similar region called the mushroom bodies (MBs), which are also important for learning and memory. Even better, fruit fly researchers have identified many of the neurons that send information to the MBs. One such example is the DPM neurons, which are critical for long-term memory storage. If the DPM neurons (there’s just two of them!) are “turned off” so that they can’t communicate with the MBs, flies can’t form long-term memories. This gave the researchers a great place to start for studying how sleep and memory are linked in the brain.

To find out if the DPM neurons are also involved in sleep, the group manipulated the activity levels of the DPM neurons and observed whether the flies showed any changes in their sleep patterns (Click here if you want to learn more about exactly how we study sleep in flies). They found that the DPM neurons had a dramatic effect: hyper-activating them increased the amount of time the flies slept, while silencing them decreased sleep (remember that silencing them also shut down long-term memory storage). Thus, sleep doesn’t just permit memory storage. These behaviors are actually tied to the same mechanism—the same neurons!—in the fruit fly brain.

The fact that DPM neurons use GABA and serotonin is another similarity to us. Those chemical promote sleep in humans too, and many sleep aids include GABA and/or serotonin supplements.

As the researchers delved further, they found that the DPM neurons were dampening part of the MBs’ activity using GABA and serotonin (both are chemical messengers that neurons use for communicating with each other). That part of the MBs was important for learning and, as it turns out, also signaling wakefulness. It’s almost as if that section of the MBs were saying “Hey, stay awake and learn this”. After a while, however, the DPM neurons may start signaling to suppress the MBs, as if to say “You’re going to need sleep if you want to remember this later”.

Finally, there was another interesting insight uncovered by this study. It is widely believed that long-term memory is stored when groups of neurons signal back and forth in an excitatory manner, progressively strengthening their connections with one another (you may have heard the adage “neurons that fire together, wire together”). Yet, the authors of this study found that the DPM neurons, which are critical for memory storage, are not actually excitatory. To the contrary, they inhibit a section of the MBs necessary for learning. What role does inhibition play in memory? This finding doesn’t answer that question, but it does demonstrate just how much work is left to be done.